Meta-analysis of two approaches to Laparoscopic Adrenalectomy: lateral transperitoneal versus posterior retroperitoneal approach

Background: Even though many studies have reported comparisons of the lateral transperitoneal adrenalectomy (LTA)and posterior retroperitoneal adrenalectomy (PRA) approaches,the conclusions were inconsistent.This meta-analysis aims at a systematic assessment of LTA and PRA. Methods: We searched MEDLINE, Pubmed, and Embase database and finally obtained 19 studies published since January 2009.Systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses. RevMan 5.3(Cochrane Collaboration) was used for data analysis. Results: 19 studies were included in the meta-analysis.The clinical characteristics of the 2 groups were similar(age, BMI, proportion of right sided, proportion of bilateral lesions,and previous abdominal surgery).There was slightly higher heterogeneity in proportion of male patients (OR 0.87, 95% CI 0.78 to 0.97, P = 0.01) and size of the tumor (MD 0.62, 95% CI 0.16 to 1.08, P = 0.008).The results confirmed that the PRA group was superior to LTA group regarding shorter operative time (MD 17.54, 95% CI 9.67 to 25.40, P < 0.0001),lower estimated blood loss (MD 37.75, 95% CI 18.08 to 57.41, P = 0.0002), shorter hospital stay (MD 1.19, 95% CI 0.76 to 1.63, P < 0.00001) and shorter time to first oral intake(MD 0.48, 95% CI 0.11 to 0.86, P =0.01).There were no statistically significant differences between LTA and PRA regarding overall complication(OR 1.37, 95% CI 0.96 to 1.97, P = 0.08),conversion to open laparotomy (OR 1.16, 95% CI 0.63 to 2.16, P = 0.63) or blood transfusion(OR 2.22, 95% CI 0.51 to 9.57, P = 0.28) . Conclusion: This meta-analysis suggests that PRA has more advantages over LTA,such as shorter operative time,lower estimated blood loss,shorter hospital stay and shorter time to first oral intake.And there were no statistically significance between LTA and PRA in terms of postoperative outcomes(total complications, conversion rates and blood transfusion).


Introduction
In the last decades,adrenalectomy has progressed from an operation to minimally invasive surgery [1] .Some patients require surgical treatment because of functional or suspected malignancy adrenal tumors [2] . Laparoscopic adrenalectomy is the preferred approach for removal of most adrenal tumors.Various studies demonstrated the safety and efficacy of laparoscopic technique.Among laparoscopic approaches,the lateral transperitoneal adrenalectomy (LTA) and the posterior retroperitoneal adrenalectomy (PRA) are common surgical procedures for the treatment of adrenal tumors.
Since first reported in 1992 [3] , LTA have been widely increased. LTA offers a wide working space for removal of larger adrenal tumors [4] . Conversely, PRA, first reported in 1995,can provides direct access to the adrenal tumor and avoids potential injury to the intra-abdominal organs. [5] Moreover, in PRA, adhesions can be avoided in patients with previous abdominal interventions, and the surgeon can treat bilateral tumors simultaneously, without changing position [6] . Currently, selection of surgical modalities for adrenal require a comprehensive consideration of the experience of surgeon,anatomical location and size of tumor [7] .
Even though many studies have reported comparisons of the two laparoscopic approaches,the conclusions were inconsistent.This meta-analysis aims at a systematic assessment of LTA and PRA.

Data sources and search
We searched MEDLINE, Pubmed, and Embase database and finally obtained 19 studies published since January 2009.Systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The following keywords were used:"transperitoneal","retroperitoneal",and "adrenalectomy". We also conducted a manual search for related articles from references to identify additional articles. All studies were extracted by two authors separately, and any divergence was resolved through consensus.

Selection criteria
Inclusion criteria were: (1) Comparison of clinical characteristics and perioperative outcomes of patients with LTA and PRA;(2) studies having full-text and relevant data were included;(3)studies published in English language;(4)All included studies provide the following data: basic characteristics of patients (age, gender [Male/ Female] ,body mass index [BMI], previous abdominal surgery), characteristics of tumor (size, side, and type of endocrine disorder), surgical outcomes (operative time, blood loss, time to oral intake, and duration of hospital stay), and postoperative outcomes (total complications, conversion, blood transfusion and mortality). The flow chart of study selection is shown in Figure1.The meta-analyses were based on published researches,so ethical approval was not required for our study.

Quality assessment
As shown in Figure 2 and Figure 3,Cochrane 'Risk of bias' assessment tool was used for quality assessment in this meta-analysis.Evaluation based on:A:Sequence generation;B:Allocation concealment;C: Blinding of participants,personnel;D: Blinding of outcome assessment;E:Incomplete outcome data;F:Selective reporting;G: Other sources of bias.All authors were involved in the quality assessment of articles included, and any divergence was resolved through consensus.Finally everyone agreed on the quality assessment.

Statistical analyses
RevMan 5.3(Cochrane Collaboration) [8] was used for data analysis.Variables were pooled only when more than 3 studies were evaluated.The odds ratio(OR) and the corresponding 95% confidence interval [CI] [8] were used to assess the differences. We considered the study present significant heterogeneity if P 0.05.Statistical heterogeneity was measured with the I 2 statistic.The randomeffects model was used when I 2 50%.
If original articles did not provide means and standard deviations (SDs) or we did not get the data we needed from authors, we used median, range, and sample size to estimate the means and SDs [9] .

Blood loss
14 studies including 1168 patients were pooled to evaluate blood loss.Significant heterogeneity was shown among studies (P<0.00001, I 2 = 97%). The results showed greater estimated blood loss in the LTA group with a random-effects model(MD 37.75, 95% CI 18.08 to 57.41, P = 0.0002) (Fig.5B).

Hospital stay
16 studies including 1466 patients were pooled to evaluate hospital stay. Length of hospital stay was significantly less in the PRA group (MD 1.19, 95% CI 0.76 to 1.63, P < 0.00001) (Fig.5C).

Time to first oral intake
6 studies including 521 patients were pooled to evaluate time to first oral intake. The results showed a significantly shorter time to first oral intake in the PRA group(MD 0.48, 95% CI 0.11 to 0.86, P =0.01) (Fig.5D).

Discussion
Laparoscopic adrenalectomy has become an accepted surgical procedure world wide for adrenal gland disease.Despite LTA has advantages of wide surgical space and familiarity of anatomy,PRA are equally effective and safe because of the superiority of direct approach to adrenal lesions [6,21,22] .Besides,PRA,which can avoid injury to abdominal organs [29] ,perhaps should be preferred for patients with a history of abdominal surgery and in bilateral adrenal lesions.
Although numerous reports have identified PRA seems more desirable compared with LTA,most of them have the disadvantage of small sample size or stringent inclusion criteria in a single-institution.
To overcome these limitations, we performed this meta-analysis.Although no difference was shown in most clinical characteristics (age, BMI, proportion of right sided, proportion of bilateral lesions,and previous abdominal surgery),the heterogeneity was found in the proportion of male patients and size of the tumor between 2 groups. Both procedures were confirmed the safety and efficacy.The results showed PRA has more advantages over LTA,such as shorter operative time ,lower estimated blood loss,shorter hospital stay and shorter time to first oral intake.The meta-analysis showed that there were no statistically significance between LTA and PRA in terms of postoperative outcomes( total complications, conversion rates and blood transfusion).
Rates of conversion to laparotomy of LTA and PRA were 3.1% (23/753) and 2.6% (16/614), respectively.And the reasons for conversion were different. Conversion occurred in LTA due to the large tumor (which could not be separated safely from the undersurface of the liver laparoscopically),

Consent for publication
Not applicable.

Availability of data and materials
The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.    Figure 1 The total flowchart